Single-cell multiomics identifies key nodes and cis-regulatory elements of the networks specifying the eye domains in zebrafish

Abstract

Congenital eye malformations result from disruptions in the early developmental programs that specify and regionalize the eye primordium. Human genetics and developmental studies in animal models have identified critical regulatory nodes within the gene regulatory networks (GRNs) patterning the distinct eye domains. However, the fundamental cis-regulatory connectivity of these networks, and their dynamic behaviour, remains poorly understood. To address these gaps, we performed a comprehensive analysis of transcriptome dynamics and chromatin accessibility at single-cell resolution in the developing zebrafish forebrain. Our single-cell multiomic approach enabled us to characterize the regulatory landscape of the main eye derivatives: neural retina, optic stalk, pigmented epithelium and lens; alongside adjacent diencephalic and telencephalic regions. We identified and functionally validated tissue-specific cis-regulatory modules, and predicted highly connected nodes within each domain. Notably, we uncovered the role of foxp1b as a conserved central node within the neural retina network, highlighting the predictive power of our analysis in reconstructing the architecture of the GRNs that specify the vertebrate eye. TeaserIdentification of central nodes and cis-regulatory networks involved in eye patterning by single-cell multiomics in zebrafish.